Zinc is essential for the growth, development and proliferation of organisms from all phyla. Its deficiency results in growth retardation and finally arrest. We have chosen Euglena gracilis as a model system to localize the critical biochemical, metabolic and structural lesions which underlie this growth arrest. Euglena gracilis grown in zinc deficient media contain increased concentrations of a number of trace metals, including manganese, magnesium, iron, copper, nickel, chromium and others, in addition to decreased zinc. Our previous studies with this organism demonstrated that several of these metals are both present in and important for DNA and RNA synthesis and function. Moreover, zinc deficiency leads to derangements in nucleic acid metabolism and to the synthesis of peptides of abnormal composition. We will use this system to examine the mutual interaction, metabolic interdependence of these metals as well as their effects on both transcription and translation. We will isolate the RNA polymerases, DNA, ribosomal, transfer and messenger RNA, ribosomes and ribosomal proteins from zinc deficient cells. We will determine the effect of metal imbalance on the structure and function of these nucleic acids, and their polymerases, as well as on the regulation of protein synthesis. These studies should provide the basis for understanding the effects of metals on nucleic acid and protein metabolism with profound implications for processes essential for cellular proliferation.